1. Field of the Invention
The invention relates generally to pharmacologically active compositions of matter comprised of snake venoms and/or snake venom fractions administered in disease mitigating quantities into the systemic circulation of mammals and particularly relates to the use of such compositions of matter for treatment of the symptomology of progressive degenerative neurological disorders, such as multiple sclerosis, amyotropic lateral sclerosis, and of the disease complex generally referred to as arthritis, particularly rheumatoid arthritis.
2. Description of the Prior Art
Various compositions of matter derived from snake venoms have previously been proposed for use in the treatment of neurological disease. In U.S. Pat. No. 4,126,676 to Sanders, neurological diseases such as amyotropic lateral sclerosis were proposed for treatment by the administration of a detoxified snake venom neurotoxin derived from the venom of the Naja genus. In U.S. Pat. No. 4,341,762 to the present inventor, compositions of matter including venoms and/or venom fractions extracted from various elapid and viperid snakes were disclosed as having pharmacological activity and having use in the treatment of the symptomology of neurological and other disorders, particularly disorders caused by malfunction of immune mechanisms. In this patent, administration in disease mitigating quantities of pharmacologically active compositions of matter comprised of snake venoms and/or snake venom fractions into the systemic circulation by subcutaneous, intramuscular or intravenous injections is described in detail for treatment of the symptomology of progressive degenerative neurological disorders, such as multiple sclerosis and amyotropic lateral sclerosis, and of the disease complex generally referred to as arthritis, particularly rheumatoid arthritis. The compositions of matter disclosed in U.S. Pat. No. 4,341,762 are also used to treat viral and autoimmune disorders by stimulation of the immune mechanisms of the body. These compositions preferably contain a neurotoxin having postsynaptic activity and which binds strongly to receptor sites of cells, and wherein reversibility of the binding is preferred. Suitable postsynaptic neurotoxins according to U.S. Pat. No. 4,341,762 are found in reptile venoms of the family Elapidae, subfamily Elapinae, and particularly the genera Naja, Ophiophagus, Dendroaspis, and others. The well-known "long" postsynaptic neurotoxin, known as .alpha.-toxin or as cobratoxin, of Naja naja siamensis (kaouthia) is particularly suited as the postsynaptic neurotoxin or receptor site "blocking agent" described in U.S. Pat. No. 4,341,762.
The compositions of matter of U.S. Pat. No. 4,341,762 also preferably include a presynaptic neurotoxin which typically inhibits the release of acetylcholine and is generally regarded as having "phospholipase activity", the presynaptic neurotoxins of choice also being relatively reversible and comprising the presynaptic neurotoxins of Bungarus multicinctus, Family Elapidae, subfamily Elapinae, these neurotoxins collectively being referred to as .beta.-Bungarotoxin. Similar presynaptic neurotoxins include Taipoxin from Oxyuranus scutellatus, Notexin from Notechis scutatus, and Crotoxin from Crotalus durissus terrificus.
The compositions of matter of U.S. Pat. No. 4,341,762 preferably are provided also with a further component comprising a venom having the capability of stimulating the immune mechanism of the body, this stimulation being considered as taught by the patent to include both the cell-mediated immune system and the interferon system, these systems being considered to be simultaneously operative in mammals. Preferred choices according to the aforesaid patent for this third component of the compositions of matter so described include venoms of the Family Viperidae, and particularly the several genera of the subfamily Crotalinae. Due to availability and suitable activity, the aforesaid patent particularly discloses the use of the venom of Agkistrodon piscivorus.
While U.S. Pat. No. 4,341,762 describes the preferred use of the whole venom for the viperid component, the present compositions of matter find particular utility in that the use thereof is accomplished without hemorrhagic effect. In particular, the removal from the viperid venom of enzymes such as L-amino acid oxidase and phosphodiesterase according to the teachings of the present invention is considered advantageous since the viperid venom fraction remaining proves to be sufficiently stimulative of the immune mechanisms and to provide physiologically active compounds which also liberate or stimulate the production of pharmacologically active substances in the body.